Browse > Article
http://dx.doi.org/10.5352/JLS.2017.27.7.834

Growth Inhibitory Effect of Extracts of Propolis on Epithelial Ovarian Cancer Cells  

Yang, Ga Ram (School of Korean Medicine, Pusan National University)
Yoon, Kyung Mi (School of Korean Medicine, Pusan National University)
Oh, Hyun Ho (School of Korean Medicine, Pusan National University)
Kim, Min Sung (Institute of Marine BioTechnology Pusan National University)
Hwang, Tae Ho (Department of Pharmacology, School of Medicine, Pusan National University)
An, Won Gun (School of Korean Medicine, Pusan National University)
Publication Information
Journal of Life Science / v.27, no.7, 2017 , pp. 834-839 More about this Journal
Abstract
Propolis is a natural product collected from plants by honey bees product used extensively in traditional medicine for its antioxidant, anti-inflammatory, immunomodulatory and anti-cancer effects. Propolis exhibits a broad spectrum of biological activities because it is a complex mixture of natural substances. Ovarian cancer is the second most common newly diagnosed cancer from all cancers among women in Korea and the leading cause of death from gynecological malignancies. While most ovarian cancer patients initially respond to surgical debulking and chemotherapy, patients later succumb to the disease. Thus, there is an urgent need to test novel therapeutic agents to counteract the high mortality rate associated with ovarian cancer. In this study, we investigated the anti-cancer properties and the active mechanism of Australian propolis in human epithelial ovarian cancer A2780 cells. Our data revealed that propolis showed a cytotoxic activity in a dose-dependent manner. Flow cytometric analysis for cell cycle arrest and apoptosis using propidium iodide staning and annexin V-FITC indicated that propolis could induce cycle arrest in the G0/G1 phase and apoptosis in a dose-dependent manner on human epithelial ovarian cancer cells. These results suggest that the Australian propolis is potential alternative agent on ovarian cancer prevention and treatment.
Keywords
A2780; anti-cancer effects; apoptosis; cell cycle arrest; propolis;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Zhuang, Y. and Miskimins, W. 2008. Cell cycle arrest in Metformin treated breast cancer cells involves activation of AMPK, downregulation of cyclin D1, and requires p27 Kip1 or p21 Cip1. J. Mol. Signal. 3, 18.   DOI
2 Zhang, L., An, R., Wang, J., Sun, N., Zhang, S., Hu, J. and Kuai, J. 2005. Exploring novel bioactive compounds from marine microbes. Curr. Opin. Microbiol. 8, 276-281.   DOI
3 Alencar, S. M., Oldoni, T. L., Castro, M. L., Cabral, I. S., Costa-Neto, C. M., Cury, J. A., Rosalen, P. L. and Ikegaki, M. 2007. Chemical composition and biological activity of a new type of Brazilian propolis: red propolis. J. Ethnoph. 113, 278-283.   DOI
4 Aletti, G. D., Gallenberg, M. M., Cliby, W. A., Jatoi, A. and Hartmann, L. C. 2007. Current management strategies for ovarian cancer. Mayo Clin. Proc. 82, 751-770.   DOI
5 Ashkenazi, A. 2008. Targeting the extrinsic apoptosis pathway in cancer. Cytokine Growth Factor Rev. 19, 325-331.   DOI
6 Awale, S., Li, F., Onozuka, H., Esumi, H., Tezuka, Y. and Kadota, S. 2008. Constituents of Brazilian red propolis and their preferential cytotoxic activity against human pancreatic PANC-1 cancer cell line in nutrient-deprived condition. Bioorg. Med. Chem. 16, 181-189.   DOI
7 Banskota, A. H., Tezuka, Y. and Kadota, S. 2001. Recent progress in pharmacological research of propolis. Phytother. Res. 15, 561-571.   DOI
8 Bast, R. C. 2003. Status of tumor markers in ovarian cancer screening. J. Clin. Oncol. 21, 200-205.   DOI
9 Choi, Y. M., Noh, D. O., Cho, S. Y., Suh, H. J., Kim, K. M. and Kim, J. M. 2006. Antioxidant and antimicrobial activities of propolis from several regions of Korea. LWT-Food Sci. Technol. 39, 756-761.   DOI
10 Chen, L., Willis, S. N., Wei, A., Smith, B. J., Fletcher, J. I., Hinds, M. G., Colman, P. M., Day, C. L., Adams, J. M. and Huang, D. C. 2005. Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol. Cell. 17, 393-403.   DOI
11 Clarke, P. G. and Clarke, S. 1995. Historic apoptosis. Nature 16, 230.
12 Ferlini, C., Raspaglio, G., Mozzetti, S., Distefano, M., Filippetti, F., Martinelli, E., Ferrandina, G., Gallo, D., Ranelletti, F. O. and Scambia, G. 2003. Bcl-2 down-regulation is a novel mechanism of paclitaxel resistance. Mol. Pharmacol. 64, 51-58.   DOI
13 Fulda, S., Gorman, A. M., Hori, O. and Samali, A. 2010. Cellular stress responses: cell survival and cell death. Int. J. Cell Biol. 2010, 214074.
14 Gottesman, M. M. 2002. Mechanisms of cancer drug resistance. Annu. Rev. Med. 53, 615-627.   DOI
15 Greenaway, W., May, J., Scaysbrook, T. and Whatley, F. R. 1991. Identification by gas chromatography-mass spectrometry of 150 compounds in propolis. Z. Naturforsch. C 46, 111-121.
16 Hunter, T. and Pines, J. 1994. Cyclins and cancer II: cyclin D and CDK inhibitors come of age. Cell 79, 573-582.   DOI
17 Piver, M. S. 2005. 16,090: the 2004 estimated US mortality from ovarian cancer. Gyneco. Oncol. 97, 301-302.   DOI
18 Jasprica, I., Bojic, M., Mornar, A., Besic, E., Bucan, K. and Medic-Saric, M. 2007. Evaluation of antioxidative activity of croatian propolis samples using DPPH. and ABTS.+ stable free radical assays. Molecules 12, 1006-1021.   DOI
19 Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., Murray, T. and Thun, M. J. 2008. Cancer statistics, 2008. CA Cancer J. Clin. 58, 71-96.   DOI
20 Pichichero, E., Cicconi, R., Mattel, M., Muzi, M. G. and Canini, A. 2010. Acacia honey and chrysin reduce proliferation of melanoma cells through alterations in cell cycle progression. Int. J. Oncol. 37, 973-981.
21 Sabatier, S., Amiot, M. J., Tacchini, M. and Aubert, S. 1992. Identification of flavonoids in sunflower honey. J. Food Sci. 57, 773-774.   DOI
22 Sawicka, D., Car, H., Borawska, M. H. and Niklinski, J. 2012. The anticancer activity of propolis. Folia Histochem. Cytobiol. 50, 25-37.   DOI
23 Seidman, J. D., Cho, K. R., Ronnett, B. M. and Kurman, R. J. 2011. Surface epithelial tumors of the ovary. In Blaustein's pathology of the female genital tract, pp. 679-784, 6th ed., Springer US.
24 Sforcin, J. M. 2007. Propolis and the immune system: a review. J. Ethnopharmacol. 113, 1-14.   DOI
25 Song, Y. H., Huh, H. Y., Kim, C. S. and Kim, K. J. 1997. Effects of propolis and caffeic acid phenethyl ester on tumorigenesis, pulmonary metastases, and activities of splenocytes and macrophages in mice. Kor. J. Immunol. 19, 617-628.
26 Szliszka, E., Czuba, Z. P., Bronikowska, J., Mertas, A., Paradysz, A. and Krol, W. 2011. Ethanolic extract of propolis augments TRAIL-induced apoptotic death in prostate cancer cells. Evid. Based Complement. Alternat. Med. 2011, 535172.
27 Vermeulen, K., Van Bockstaele, D. R. and Berneman, Z. N. 2004. The cell cycle: A review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif. 36, 131-149.
28 Willis, S. N., Fletcher, J. I., Kaufmann, T., van Delft, M. F., Chen, L., Czabotar, P. E., Ierino, H., Lee, E. F., Fairlie, W. D., Bouillet, P., Strasser, A., Kluck, R. M., Adams, J. M. and Strasser, A. 2007. Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science 315, 856-859.   DOI
29 Jung, B. I., Kim, M. S., Kim, H. A., Kim, D., Yang, J., Her, S. and Song, Y. S. 2010. Caffeic acid phenethyl ester, a component of beehive propolis, is a novel selective estrogen receptor modulator. Phytother. Res. 24, 295-300.
30 Kalil, N. G. and McGuire, W. P. 2002. Chemotherapy for advanced epithelial ovarian carcinoma. Best Pract. Res. Clin. Obstet. Gynaecol. 16, 553-571.   DOI
31 Kim, A., Ueda, Y., Naka, T. and Enomoto, T. 2012. Therapeutic strategies in epithelial ovarian cancer. J. Exp. Clin. Cancer Res. 31, 14.   DOI
32 Lee, H. S., Lee, J. Y., Kim, D. C., In, M. J. and Hwang, W. I. 2000. The inhibitory effects of propolis on in vitro proliferation of human cancer cell lines. Kor. J. Nutr. 33, 80-85.
33 Mozzetti, S., Ferlini, C., Concolino, P., Filippetti, F., Raspaglio, G., Prislei, S., Gallo, D., Martinelli, E., Ranelletti, F. O., Ferrandina, G. and Scambia, G. 2005. Class III ${\beta}$-tubulin overexpression is a prominent mechanism of paclitaxel resistance in ovarian cancer patients. Clin. Cancer Res. 11, 298-305.
34 Li, F., Awale, S., Tezuka, Y. and Kadota, S. 2010. Cytotoxicity of constituents from Mexican propolis against a panel of six different cancer cell lines. Nat. Prod. Commun. 5, 1601-1606.
35 Liu, Z., Zhu, G., Getzenberg, R. H. and Veltri, R. W. 2015. The upregulation of PI3K/Akt and MAP kinase pathways is associated with resistance of microtubule‐targeting drugs in prostate cancer. J. Cell Biochem. 116, 1341-1349.   DOI
36 Meher, P. K. and Mishra, K. P. 2017. Radiation oxidative stress in cancer induction and prevention. J. Radiat. Cancer Res. 8, 44-52.   DOI